Description

Diazepam (Valium) is a benzodiazepine used to treat anxiety, alcohol withdrawal, and muscle spasms. It may also be used to treat seizures, insomnia, and other conditions as determined by your doctor. Anxiolytic, Sedative, Muscle Relaxant.

Pharmacology

Diazepam (Valium) is a benzodiazepine with CNS depressant properties and a somewhat flatter dose-response slope than the sedative-hypnotic drugs.

In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with diazepam do have transient ataxia at higher doses. Diazepam was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Injections into animals have produced localized irritation of tissue surrounding injections and some thickening of veins after intravenous use.

Indications and Usage

Diazepam (Valium) is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.

Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; stiff-man syndrome; and tetanus.

The effectiveness of diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Warnings

Usage in Pregnancy: An increased risk of congenital malformations associated with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may become pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.

Diazepam is not of value in the treatment of psychotic patients and should not be employed in lieu of appropriate treatment. As is true of most preparations containing CNS-acting drugs, patients receiving diazepam should be cautioned against engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle.

As with other agents which have anticonvulsant activity, when diazepam is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of diazepam in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures.

Since diazepam has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during diazepam therapy.

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines.

Precautions

If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed - particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression; particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. The usual precautions in treating patients with impaired renal or hepatic function should be observed.

In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially, to be increased gradually as needed and tolerated).

Information for the Patient: To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.

Drug dependence: Abrupt cessation of large doses of diazepam after prolonged periods may precipitate acute withdrawal symptoms and, in these cases, the drug should be discontinued gradually. Caution should be exercised when it is considered necessary to administer diazepam to addiction prone individuals.

Until additional information is available, injectable diazepam is not recommended for obstetrical use.

Injectable diazepam has produced hypotension or muscular weakness in some patients particularly when used with narcotics, barbiturates or alcohol.

Drug Interactions

If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed - particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression; particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. The usual precautions in treating patients with impaired renal or hepatic function should be observed.

In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially, to be increased gradually as needed and tolerated).

The clearance of diazepam and certain other benzodiazepines can be delayed in association with cimetidine (Tagamet) administration. The clinical significance of this is unclear.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. This includes clozapine, disulfiram, lithium, omeprazole, valproic acid, and medicines used to treat moderate to severe pain and HIV infection. Inform your doctor of any other medical conditions, allergies, pregnancy, or breast-feeding.

Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance.

Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy.

Drug Abuse and Dependence:

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of diazepam. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Overdose

Signs and Symptoms

Drowsiness, oversedation and ataxia. When the effects of drug overdosage begin to wear off, the patient exhibits some jitteriness and overstimulation. The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimum effects on respiration, pulse and blood pressure unless the overdosage is extreme.

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

Manifestations of diazepam overdosage include somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol (Levophed) or metaraminol (Aramine). Dialysis is of limited value. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.

Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with benzodiazepine is known or suspected.

Dosage

Do not exceed the recommended dosage or take this medicine for longer than prescribed. Exceeding the recommended dose or taking this medicine for longer than prescribed may be habit forming.

Follow the directions for using this medicine provided by your doctor.

Store this medicine at room temperature, away from heat and light.

If you miss a dose of this medicine and you are using it regularly, take it as soon as possible. If you do not remember until later, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

Dosage should be individualized for maximum beneficial effect.

Adults: Symptomatic relief of anxiety and tension in psychoneurosis and anxiety reactions: 2 to 10 mg, 2 to 4 times daily depending upon severity of symptoms.

Symptomatic relief in acute alcohol withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed.

Adjunctively for relief of skeletal muscle spasms: 2 to 10 mg, 3 to 4 times daily.

Elderly and debilitated patients, or in the presence of debilitating disease: 2 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated.

Children: (Because of varied responses, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months): 1 to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated.

Do not prescribe or administer diazepam for periods in excess of 6 weeks, unless a definite need for utilizing this medication has been established by a followup medical examination.

How Supplied

Diazepam Tablets USP, 5 mg are available as yellow, round, flat faced, beveled edge tablets, debossed "Z" and "3926" with a bisect on one side and "5" on the other side containing 5 mg diazepam USP

as follows:

Manfactured by Ivax Pharmaceuticals

Repackaged and Distributed for private label by Apotheca, Inc.

12634-529-91 Blister Pack UD of 1

12634-529-55 Blister Pack Card of 15

12634-529-96 Bottle of 6

12634-529-80 Bottle of 20

Diazepam Tablets USP,10 mg are available as blue, round, flat-faced, beveled-edge, bisected tablet. Debossed with stylized Barr on one side and 555/164 on the other side containing 10 mgdiazepam USP as follows:

The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse. Last updated 3/03.